The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production.
NF-ATc1 is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In activated T cells, nuclear NF-AT binds to the promoter regions of multiple cytokine genes and induces their transcription. The role of NF-ATc1 was investigated in recombination activating gene-1 (RAG-1)-deficient blastocyst complementation assays using homozygous NF-ATc1-/- mutant ES cell lines. NF-ATc1-/-/RAG-1-/- chimeric mice showed reduced numbers of thymocytes and impaired proliferation of peripheral lymphocytes, but normal production of IL-2. Induction in vitro of Th2 responses, as demonstrated by a decrease in IL-4 and IL-6 production, was impaired in mutant T cells. These data indicate that NF-ATc1 plays roles in the development of T lymphocytes and in the differentiation of the Th2 response.
Yoshida
H
H
The Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Nishina
H
H
Takimoto
H
H
Marengère
L E
LE
Wakeham
A C
AC
Bouchard
D
D
Kong
Y Y
YY
Ohteki
T
T
Shahinian
A
A
Bachmann
M
M
Ohashi
P S
PS
Penninger
J M
JM
Crabtree
G R
GR
Mak
T W
TW
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018398:Homeodomain Proteins; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000276:immunology / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C064658:RAG-1 protein